Targeted immunotherapy has thus emerged as promising field of research in the treatment of malignancies and has received a great deal of interest in recent years (Carpentier and Meng, 2006, Curr Opin Oncol, 18(6):631-636; Wainwright et al., 2012, Exp Opin Emerging Drugs; 17(2):181-202). One of the most extensively studied targets is the interleukin-13 receptor alpha 2 (IL13Rα2) (Thaci et al., 2014, Neuro-Oncol, 16(10):1304-1324). IL13Rα2 is a decoy receptor for interleukin-13 (IL13), lacking the signaling chain that is present on the ubiquitous IL13Rα1, thus preventing any IL13-mediated downstream signaling pathway (Arima et al., 2005, J Biol Chem, 280(26):24915-24922). Increased expression of IL13Rα2 has been reported to promote tumor progression in glioma and other tumor models. IL13Rα2 expression is a prognostic marker for glioma malignancy grade and for poor patient survival (Brown et al., 2013, PLoS ONE, 8(10): Article ID e77769). Its selective expression on MG, discovered almost two decades ago, has been a target for therapy ever since (Debinski et al., 1999, Clin Canc Res, 5(5):985-990).
Glioblastoma is the most common primary brain tumor in adults. More than half of the 18,000 patients diagnosed with malignant primary brain tumors in US each year have glioblastoma multiforme. Glioblastoma multiforme is an anaplastic, highly cellular tumor, with high proliferation indices, microvascular proliferation and focal necrosis. Signs and symptoms depend on several factors (size, rate of growth, localization of the tumor within the brain) and are mainly represented by headache, seizures, neurological deficits, changes in mental status. Glioblastoma multiforme prognosis remains dismal. Survival time is less than 2 years for the majority of patients.
Despite incremental improvements in survival with the current standard of care for glioblastoma (GBM), which is a tripartite regimen of surgery, radiotherapy, and chemotherapy (Rolle et al., 2010, Neurosurgery Clin of North America, 21(1):201-214; Ashby and Ryken, 2006, Neurosurgical focus, 20(4):E3), the prognosis for most patients remains dismal (Stupp et al, 2009, Lancet Oncol, 10(5):459-466; Omuro and DeAngelis, 2013, JAMA, 310(17):1842-1850). Major limitations in the treatment of GBM are the tumor's location within the brain that impedes delivery of cytotoxic agents across the blood-brain barrier (Ashby and Ryken, 2006, Neurosurgical Focus, 20(4):E3), compounded with a strong immunosuppressive environment (Rolle et al., 2012, Adv Exp Med Biol, 746:53-76) and chemo- and radioresistant glioma-initiating cells (Bao et al, 2006, Nature, 444(7120):756-760; Frosina, Mol Canc Res, 2009 7(7):989-999). As a result, novel strategies are continually being tested to improve patient survival, quality of life, and overall outcomes.
Accordingly, described herein are compositions and methods for more efficacious treatment of cancers in which malignant cells express or over-express IL13Rα2, including brain cancers.